MspTL is the major surface protein of Treponema lecithinolyticum associated with periodontitis and endodontic infections. Our recent investigation revealed that MspTL induces proinflammatory cytokines and intercellular adhesion molecule 1 in THP-1 cells and periodontal ligament cells. In this study we conducted oligonucleotide microarray analysis to investigate the global transcriptional regulation in THP-1 cells stimulated with purified recombinant MspTL. MspTL upregulated the expression of 90 genes in THP-1 cells at least four fold, and the functions of these genes were categorized into adhesion, apoptosis/antiapoptosis, cell cycle/growth/differentiation, chemotaxis, cytoskeleton organization, immune response, molecular metabolism, proteolysis, signaling, and transcription. The majority of the modified genes are known to be NF-κB-responsive and interferon-stimulated genes (ISGs). The expression of 12 selected genes was confirmed by real-time RT-PCR. Because prostaglandin E2 (PGE2) is an important inflammatory mediator and Cox-2 was found to be induced by MspTL in the microarray analysis, we determined the level of PGE2 in the culture supernatants of MspTL-treated cells and found that MspTL significantly increased PGE2. Our results provide insight into the gene regulation of host cells in response to MspTL, and may contribute to the understanding of the molecular mechanism in periodontitis.